Brest, meanwhile, narrowly survived relegation last season; like their forthcoming opponents, they have reacted by making a change in the dugout.
Match preview
Indeed, after missing out on Champions League qualification by finishing fourth last season, Lyon parted ways with Rudi Garcia after two promising but ultimately disappointing seasons.
The former Roma boss guided Lyon to the Champions League semi-final within six months of being appointed in November 2019, and looked set to lead Les Gones to their first Ligue 1 triumph since 2008 after an incredibly strong start last season.
However, their form declined during the second half of the campaign, unlike Lille, Paris Saint-Germain and Monaco, who all ended up flying past them in the league table.
Former Bayer Leverkusen manager Peter Bosz has been handed the reigns, which may not fill Lyon fans with a great deal of confidence given that the 57-year-old's time at Leverkusen followed a similarly topsy-turvy trajectory to Garcia's in Lyon.
Bosz is yet to receive any financial backing in the transfer market, too, and has lost the club's star player Memphis Depay to Barcelona.
Regardless, he will still be expected to guide his players past challenges of the calibre of Brest, but more incomings may be required if they are to be confident of returning to Europe's elite competition.
As mentioned, after surviving relegation by a solitary point and position on a dramatic final day last season, Brest have chosen to replace Olivier Dall'Aglio with former Montpellier manager Michel Der Zakarian.
The 58-year-old, who enjoyed a playing career spanning almost 20 years exclusively in France, brings a wealth of experience with him into the role, having previously managed Nantes, Clermont and Reims.
To his credit, Montpellier finished in the top half in each of his four seasons in charge, suggesting that he could be the man to guide Brest away from danger and into a more comfortable position in the table.
Talented left-back Romain Perraud has departed the club for Southampton for around £10m, but Finland international Jere Uronen represents a decent replacement having impressed for his country during Euro 2020.
It remains to be seen whether Der Zakarian will see any more of the Perraud fee in terms of improving the squad, but either way he will likely be confident in both his own and his players' abilities that they can avoid facing any serious jeopardy again, even if they have been handed a very tough start to the season in Lyon on Saturday.
Team News
Lyon will start the season without Jeff Reine-Adelaide and Lenny Pintor after both players suffered cruciate ligament ruptures in February earlier this year.
Karl Toko Ekambi and Islam Slimani both scored in the 5-3 friendly defeat to Porto last weekend, so Garcia could look to those two and Tinotenda Kadewere as his first-choice front three for the coming campaign.
Bruno Guimaraes will almost certainly be a key part of the new manager's plans, too, but he is unavailable due to his involvement at the Tokyo Olympics for Brazil Under-23s.
Brest have two long-term absentees of their own in the shape of Paul Lasne and Sebastien Cibois, who are recovering from serious cruciate ligament and Achilles' tendon injuries respectively.
Uronen should make his competitive debut for the club at left-back, with Kadewere certainly representing a tough first assignment in his new surroundings.
Marco Bizot has arrived from AZ Alkmaar in recent days to provide more competition between the sticks, but Der Zakarian will likely provide Gautier Larsonneur with a chance to make the goalkeeping position his own, at least until Cibois's return.
Lyon possible starting lineup:
Lopes; Dubois, Marcelo, Denayer, Cornet; Caqueret, Aouar; Kadewere, Paqueta, Ekambi; Slimani
Brest possible starting lineup:
Larsonneur; Faussurier, Brassier, Chardonnet, Uronen; Faivre, Magnetti, Belkebla, Cardona; Honorat, Mounie
We say: Lyon 1-1 Brest
With Lyon missing one or two key players and beginning life without Depay, we can envisage a surprise result here, with Brest potentially gaining a positive result from the game.
Der Zakarian is a very promising managerial appointment for the club having impressed at Montpellier; while this is a tougher challenge for him, a flying start would certainly help matters no end.